Vasodilators such as nifedipine have been used to open the vascular system and permit the freer flow of blood. Coronary vasodilators are thus useful in the treatment of angina pectoris. Peripheral vasodilators find utility in lowering blood pressure and thus are used in the treatment of hypertension. However, peripheral vasodilation may result in reflex tachycardia whereby the heart rate is speeded up to compensate for, and thus neutralize the effect of, the loss of blood pressure. An object of the invention is a peripheral vasodilator useful in treating hypertension which does not result in reflex tachycardia or other undesireable actions of the heart.
Milrinone is a bipyridine inotropic agent which has been investigated for use in improving cardiac function in patients with congestive heart failure. The primary mechanism of this agent has been thought to be improvement in left ventricular systolic function whereby the contractile forces in the heart are strengthened. However, it is recognized by E. S. Monrad et al in Circulation, Vol. 70, No. 6, pp 1030-1037 (1984) that improved diastolic function may contribute to the beneficial effect of this drug. Milrinone and its use as a cardiotonic, e.g. in treating congestive heart failure, is taught in U.S. Pat. Nos. 4,313,951 and 4,413,127. It is also an object of this invention to provide a "lusitropic" agent useful in the treatment of congestive heart failure which acts through the mechanism of improved myocardial relaxation in the diastolic portion of the heart rhythm.
Dihydropyridines having ester moieties at the 3-position are taught in European Patent 291,799 and German DE 3,712,371 and DE 3,724,909.